Glasgow University will spend at least £80m on new buildings and equipment and £55m on refurbishing facilities over the next five years.
And it will take over 10 acres of the site of the Western Infirmary, which is moving to the new South Glasgow Hospital in 2015.
Education bosses will hold a public consultation to help decide what to do with the extra land.
Professor Anton Muscatelli, principal and vice-chancellor of the university said: "This is as significant a development, in the on-going story of the University of Glasgow, as the relocation to Gilmorehill from the city centre was in 1870.
"The acquisition of the site will allow us a unique opportunity to provide modern, fit-for-purpose facilities that are in keeping with Glasgow's status as a world-leading research-intensive university."
The university has already secured most of the ground bordered by Dumbarton Road, Church Street and University Avenue from NHS Greater Glasgow and Clyde.
Talks are continuing to secure a remaining part of the site, giving the entire 14 acres for university use.
Glasgow University staff, students, local residents, businesses and other interest groups are being asked what they think should be done with the site.
There will be talks with Glasgow City Council, NHS Greater Glasgow and Clyde, the Scottish Government and Scottish Enterprise.
Council chief Gordon Matheson said: "The acquisition of this site by the university would present an opportunity to develop state-of-the art facilities that would consolidate and develop the city's status as a leader in education, renewables, research and technology."
The university is also reviewing how best to use buildings on the Gilmorehill campus.
The redevelopment is aimed at developing a sustainable estate, including ambitious carbon footprint reduction targets.
Mr Muscatelli added: "We now have an opportunity to create a lasting legacy for future generations of students, academics, local people and for the city of Glasgow as whole.
"Over the next 10 years as we develop the Gilmorehill site we anticipate investing more in our infrastructure than was spent in delivering the 2014 Glasgow Commonwealth Games and so create something very special for our university community and the City of Glasgow."
Consultation events are to be held at the University Welcome Point tomorrow from 10am to 7pm and at Hillhead Library on Monday between 4pm and 8pm.
Robert Calderwood, chief executive, NHS Greater Glasgow and Clyde, said: "In 1878 the university transferred the land to the former Hospital Authority to construct the original Western Infirmary.
"The terms of that deal stipulated that should the site no longer be required for healthcare purposes, the university should be given the opportunity to re-acquire it.
"We are delighted that a significant part of the site has already been sold back."
For more on the plan visit www.gla.ac.uk/ campusdevelopment